In order to improve understanding of the effects of chemotherapy on human leukemic and normal bone marrow cells, in vitro cell-kill by chemotherapeutic agents will be quantitatively studied using 2 comparable cell-culture methods: one is the newly developed culture method with the unique feature of daily feeding for assay of clonogenic human leukemic cells (L-CFU); the other is the established agar culture method for the assay of normal myeloid precursor cells (CFU-C). Bone marrow cells will be exposed to the graded doses of the chemotherapeutic agents in vitro for 2 hours in an incubator, and then washed free of the drugs before culture for the surviving fractions of L-CFU or CFU-C. From the dose survival curves thus obtained, quantitative parameters to express chemotherapy sensitivity and synergism of combination chemotherapy will be derived. Using these parameters as guidelines, more effective in vitro chemotherapy regimens will be searched systematically. Also in vitro parameters will be correlated with in vivo response to chemotherapy to find reliable in vitro predictive systems for in vivo response. Cell kinetic studies to be done on clonogenic cells will further elucidate the mechanism of action of chemotherapy. These studies will enable us to formulate more effective and rational clinical chemoterapy regimens for human leukemia. This approach using assays for clonogenic cells, has been used in animal tumor successfully, but is new for the primary explant human tumor, and will be the model for future studies in human solid tumors.